Vascular embolization often is the chosen method for controlling bleeding in the blood vessels or occluding blood supply to solid mass tumors or vascular aneurysms. Currently available therapeutic regimens for treating solid mass tumors can be difficult to administer, particularly depending on the properties of the embolic, or bulking, composition used. Aneurysms, arteriovenous malformations (“AVMs”) and other vascular abnormalities, for example, vascular tumors, can be difficult to treat. Treatment of lesions and growths that occur in the brain or brain stem is especially complicated due to the particularly sensitive nature of the surrounding tissue.
Cyanoacrylate adhesives have been used for treatment of AVMs and other vascular abnormalities for almost thirty years. The usefulness of these compositions has been limited by cytotoxicity and the amount of heat generated by polymerization. Recent developments in the formulation of cyanoacrylate compositions have improved the usefulness of such compositions in treating vascular disease. For example, U.S. Pat. No. 6,015,541, issued Jan. 18, 2000, describes a radioactive composition for treating solid mass tumors comprising a biocompatible free polymer, a biocompatible solvent, and about 0.1 to about 25 weight percent of a water in soluble radioisotope. The biocompatible polymer can be a cyanoacrylate free polymer variant and the composition contains n-butyl-2-cyanoacrylate (NBCA) in combination with an iridium isotope. Although such a composition was demonstrated to have effect on a solid mass tumor in a rabbit, the viscosity and suspension properties of the composition were less than desirable. Another disadvantage is that the iridium isotope settled within several seconds after mixing, requiring constant, gentle agitation to prepare a prolonged suspension.
A composition including 2-hexyl cyanoacrylate and gold was described in U.S. Pat. No. 6,037,366, issued Mar. 14, 2000. The cyanoacrylate composition demonstrated improved cohesion properties compared to previous compositions. Administration of such compositions involved mixing two separate components of material immediately prior to administration into the AVM. One component contained cyanoacrylate liquid monomer containing pure phosphoric acid hydroquinone and p-methoxyphenol. The second component contained pure powdered gold, a small amount of pre-polymerized cyanoacrylate polymer and a fatty acid, ethyl myristate. The improved cohesion properties kept the materials together during the time required for polymerization. Although incorporation of a small amount of pre-polymerized cyanoacrylate monomer is mentioned in the composition, there is no mention of any non-cyanoacrylate rheology or viscosity modifying agent.
Alkyl cyanoacrylate compositions in general were described in International PCT publication WO 00/44287, published on Aug. 3, 2000. The compositions contained the alkyl cyanoacrylate and at least one inhibitor, and a second component comprised of a resultant aggregate structure formed from an alkyl cyanoacrylate monomer, an alkyl esterified fatty acid and an opacificant agent. The composition formed the resultant aggregate structure upon contact with blood. Although these compositions demonstrate improved properties over prior compositions, inadvertent tissue adhesion to microcatheter delivery devices used to administer such compositions remains a problem. There is no suggestion or recognition that such properties can be improved by a non-cyanoacrylate rheology modifying agent.
Accordingly, there remains a need for an improved composition for treating vascular abnormalities, such as AVMs or brain aneurysms. The improved composition would have properties of apparent viscosity between 25 cP and 2000 cP, improved cohesiveness, improved suspension of dense radiopacifier powders, and radiopacity. In addition, the composition would form a solid composition possessing improved hydrolytic stability upon contact with an aqueous environment, for example, blood.